knuckle (n.) Look up knuckle at Dictionary.com
mid-14c., knokel "finger joint; any joint of the body, especially a knobby one; morbid lump or swelling;" common Germanic (cognates: Middle Low German knökel, Middle Dutch cnockel, German knöchel), literally "little bone," a diminutive of Proto-Germanic root *knuck- "bone" (compare German Knochen "bone).

As a verb from 1740, originally in the game of marbles. To knuckle down "apply oneself earnestly" is 1864 in American English, extended from marbles (putting a knuckle on the ground in assuming the hand position preliminary to shooting); to knuckle under "submit, give in" is first recorded 1740, supposedly from the former more general sense of "knuckle" and here meaning "knee," hence "to kneel." The face-busting knuckle-duster is from 1858 (a duster was a type of protective coat worn by workmen).